Concurrent platinum-based chemotherapy and thoracic radiation treatment (RT) has become a standard of care in the treatment of unresectable non-small cell lung cancer (NSCLC). This treatment methodology is based on studies published in the 1980's that demonstrated a survival benefit in NSCLC with the addition of sequential chemotherapy to RT alone, and further studies from the 1990's demonstrating a 3-4 month improved median survival time with the use of chemotherapy and RT concurrently.

Median survival with platinum-based chemotherapy and concurrent thoracic RT has been demonstrated to be 15-17 months by several groups, including the Southwest Oncology Group (SWOG) in their study 9410.

A further SWOG study, 9504, examined the addition of docetaxel maintenance chemotherapy following concurrent cisplatin, etoposide, and thoracic RT for patients with locally advanced NSCLC. SWOG 9504 was a single-arm, phase II study, which demonstrated a median survival time of 26 months. Since the publication of this data, taxane-based consolidation chemotherapy has become widely used in treatment of unresectable NSCLC following concurrent chemotherapy and RT.

This phase III trial was carried out to evaluate outcomes with the addition of docetaxel maintenance treatment to concurrent cisplatin, etoposide, and thoracic RT.

Materials and Methods

This phase III clinical trial was designed to enroll 259 patients, with planned randomization of 180, to demonstrate an improvement in median survival time (MST) from 15 months to 25 months with 80% power.

Inclusionary criteria included stage IIIA or IIIB NSCLC deemed unresectable, ECOG performance status 0-1 at time of enrollment (0-2 at time of randomization), FEV1 > 1L, and <5% weight loss.

All patients were treated with cisplatin, 50 mg/ m2, on days 1, 8, 29, 36, and etoposide, 50 mg/m2, on days 1-5 and 29-33. Concurrent with chemotherapy, patients received thoracic RT to a total dose of 5940 centigray.

Three-year overall survival (OS) was 28% in the observation group versus 27% in the docetaxel group (p = 0.9).

Incidence of grade 3-4 infection was 8.9% for the whole group during concurrent chemoradiation treatment,11% in the docetaxel arm, and 0% in the observation arm. Incidence of treatment-related death was 1.5% during concurrent chemoradiation, 5.5% during docetaxel maintenance, and 0% during observation.

28.8% of patients randomized to docetaxel maintenance were hospitalized during their treatment versus 8.1% of patients randomized to observation.

Author's Conclusions

MST in both arms of this trial was higher than has been historically described

This trial showed an improvement in MST, PFS, and 3-year OS when compared to historical controls. Improved patient selection with increased availability of PET and MRI scan may contribute to this by allowing elimination of patients with occult stage IV disease from the trial. Still, MST and OS were moderately reduced in this study when compared to the SWOG 9504 phase II trial. The authors note that this may be due to more rigorous requirements for pulmonary function in SWOG 9504 versus this trial (FEV1 > 2 L versus FEV 1 ≥ 1 L, respectively).

This trial showed no overall survival benefit with the addition of docetaxel maintenance to concurrent chemoradiation. Given the significant increase in toxicity described in this study, maintenance taxol-based chemotherapy should likely not be used for patients with unresectable stage III NSCLC after definitive, concurrent, platinum-based chemoradiation outside of a clinical trial.